Asthma is characterized by airway hyper-responsiveness and chronic airway inflammation1. Large numbers of eosinophils and T lymphocytes infiltrate peribronchial tissues in asthmatics2, trafficking into the lung an increased capacity to generate cysteinyl leukotrienes (CysLT's) and TH2 cytokines1, 3, 4. CysLT's have been associated with the asthmatic diathesis in both experimental models and patients with asthma5, 6. One of the many actions of TH2 cytokines is to up-regulate the expression of biosynthetic enzymes for eicosanoids—including leukotrienes and lipoxins (LX's)7, 8.
LX's are a separate class of eicosanoids that are distinct in structure and function7, and their biosynthesis is temporally dissociated from the formation and impact of other eicosanoids9. LX's are generated in human tissues, including airways10. LX's carry unique counter-regulatory actions that inhibit CysLT-mediated vascular responses11 and promote resolution of cytokine-driven acute inflammation9. When administered to human cells in vitro or murine systems in vivo, at least two classes of receptors, CysLT1 receptors and LXA4 receptors (designated ALX), can interact with LX's to mediate their actions12, 13. A role for LX's in asthma has not yet been directly evaluated in well-qualified experimental animal models.
The global prevalence of asthma continues to increase, affecting millions of peoples' daily lives, but treatment is far from ideal18. Clinical responses to current therapies, such as inhaled corticosteroids and leukotriene modifiers are heterogeneous19 and even with optimal treatment there is a substantial burden of unaddressed disease.
With further evidence for serious toxicity from exogenous corticosteroids, new anti-inflammatory strategies are needed for asthma and other allergic illnesses.